Thymoquinone attenuates rheumatoid arthritis by downregulating TLR2, TLR4, TNF-α, IL-1, and NFκB expression levels

Abstract

Background Thymoquinone (TQ), the most important active principle of Nigella sativa is known to have anti-inflammatory, analgesic, antimicrobial and antioxidant properties.

Aim The present study was designed to see the anti-arthritic effect of TQ in rat model of arthritis.

Methods In the current research, anti-arthritic effect of TQ was determined in Freund’s Complete Adjuvant (FCA)-induced arthritic rats by measuring TLRs expression levels. The mRNA expression levels of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), interleukin-1 (IL-1), nuclear factor-kappa B (NFκB) and tissue necrosis factor-α (TNF-α) were measured by reverse-transcription polymerase chain reaction. Arthritic signs were observed by macroscopic criteria. Hematoxylin and Eosin staining was used to perform ankle joint histopathology and agglutination method was used for measuring C-reactive protein (CRP) levels. Rheumatoid factor, alanine transaminase, aspartate aminotransferase, urea and creatinine were also determined in serum.

Results TQ treatment reduced the macroscopic arthritic score, levels of CRP, synovial inflammation, pannus formation and bone erosion. It also reduced the mRNA levels of TLR2, TLR4, IL-1, NFκB and TNF-α. Methotrexate, used as a reference drug also significantly decreased their expression levels. TQ also normalized the hematological markers and did not depict any signs of hepatotoxicity and nephrotoxicity as determined by serum levels of alanine transaminase, aspartate aminotransferase, urea and creatinine. Our results showed that TQ possesses significant anti-arthritic activity which can be due to its anti-inflammatory and immunomodulatory effects.

Conclusion Results indicate that TQ has got the potential to ameliorate rheumatoid arthritis by downregulating TLR2, TLR4, TNF-α, IL-1, and NFκB expression levels.